Combined effect of nicotinamide and streptozotocin on diabetic status in partially pancreatectomized adult BALB/c mice.

Pancreatic regeneration after pancreatectomy has been well documented in the animal models. We have recently reported that STZ diabetic animals operated for partial pancreatectomy showed normoglycemic status after the operation as compared to uncontrolled hyperglycemia and even death in the diabetic sham operated animals. In drug and virus-induced experimental diabetic models there is a high mortality of animals due to uncontrolled destruction of the beta-cells. In order to destroy sufficient beta-cell mass so as to induce diabetes but prevent mortality, we designed present studies to investigate the combined effect of pancreatectomy, nicotinamide, and streptozotocin (STZ) on diabetic status of BALB/c mice. BALB/c mice of either sex were subjected to 50% pancreatectomy. These were then treated with nicotinamide (350 mg/kg body weight) before and after streptozotocin (200 mg/kg body weight) administration. The changes in body weight, blood glucose levels, serum and pancreatic insulin contents of these animals were monitored in experimental and control group for 12 weeks, and follow up studies were made of these animals for further 12 weeks. It was found that there was a drastic loss of body weight, decreased serum and pancreatic insulin levels coupled with sustained and low levels of hyperglycemia in the experimental group as opposed to the control group. The results indicate that partial pancreatectomy followed by nicotinamide and streptozotocin treatment leads to a long-lasting hyperglycemic state, depicting the clinical symptom of NIDDM without mortality. The study probably reveals a new model for experimental diabetes.     

Metabolic effects of partial pancreatectomy in the Northern pike, Esox Indus L.

Metabolic effects of partial pancreatectomy (70%) after 1 month were studied in the Northern pike, Esox lucius L. Plasma protein and haematocrit levels were significantly reduced in the pancreatectomised fish when compared with sham-operated controls. By contrast, however, blood glucose, plasma amino acid nitrogen and cholesterol levels remained unaltered.
The tolerance to intra-arterial glucose and amino acid loading was compared in pancreatectomised and control fish. Pancreatectomy resulted in a significantly impaired clearance of amino acids from the plasma whereas glucose tolerance was similar in both groups. Neither glucose nor ketones could be detected in the urine of pancreatectomised pike after 1 month. These data indicate that partial pancreatectomy does not cause the development of a diabetic state in this species over a 1 month period.     

Protective Effects of Moderate Intensity Static Magnetic Fields on Diabetic Mice

The purpose of this study was to investigate the effects of moderate-intensity static magnetic field (SMF) on diabetic mice. We studied the effects of SMF on blood glucose of normal mice by starch tolerance and glucose tolerance tests. Then, we evaluated the effects of SMF on blood glucose of diabetic mice by establishing alloxan-induced type 1 diabetic mice and high-fat diet + streptozotocin (STZ)-induced type 2 diabetic mice. The results showed that different magnetic field intensities and blank control did not affect the blood glucose of normal mice. After starch and glucose administration, different magnetic fields could improve the glucose tolerance of normal mice, and this was obvious in the 600 mT group. In the experiment of type 1 diabetic mice induced by alloxan, the results showed that different magnetic field intensities could improve the starch tolerance of mice, and that in the 400 mT group was obvious. In the experiment of type 2 diabetic mice induced by a high-fat diet + STZ, the 400 mT group could reduce food intake and water consumption in the later period. The 600 mT group could improve the starch tolerance of mice. The 400 and 600 mT groups could reduce fasting blood glucose. At the same time, total cholesterol and triglyceride decreased in different magnetic field intensities, and the 600 mT group could significantly increase the serum insulin content of mice. In summary, the results of this study suggest that SMF has a protective role in diabetic mice. Bioelectromagnetics. © 2020 Bioelectromagnetics Society     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

Experimental diabetes in cats induced by partial pancreatectomy alone or combined with local injection of alloxan

Experimental diabetes was produced in cats by partial pancreatectomy using a short and technically simple surgical procedure. Electrocautery was used to cauterize pancreatic blood vessels and seal free edges of remaining pancreatic tissue to prevent secretion of pancreatic enzymes into the peritoneal cavity. In a second group of animals, partial pancreatectomy was followed by local injection of alloxan into an arterial branch of the cranio-mesenteric artery. The combined procedure resulted in diabetes mellitus in 100% (8 of 8) animals as compared to only 70% (14 of 20) in those subjected to partial pancreatectomy alone. In addition, the alloxan-pancreatectomized cats had a reduced latency period prior to onset of chronic hyperglycemia (4.8 days compared to 19.3 days postoperatively in pancreatectomized cats). The diabetic cats were maintained in poor metabolic control (blood glucose approximately 300 mg/dl) by daily injections of low doses of long-acting insulin. Pancreatic enzyme supplementation was given by mouth. Weight changes and blood glucose levels were monitored carefully to maintain the health of the animals while keeping them in poor metabolic control.     

Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats

Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.     

小檗碱对2型糖尿病ICR小鼠模型的治疗作用

目的比较小檗碱及小檗碱与添加剂对2型糖尿病ICR小鼠模型的降糖、降脂效果。方法100只三周龄雄性ICR小鼠随机分为正常组、模型组、小檗碱组、小檗碱加低剂量添加剂组、小檗碱加高剂量添加剂组及二甲双胍组,以高糖高脂加尿链佐菌素诱导小鼠2型糖尿病模型,并分别以小檗碱、小檗碱加低剂量添加剂、小檗碱加高剂量每天灌胃干预治疗6周。检测血糖、血清血脂、肾功指标的变化情况;给药前后做糖耐量胰岛素耐量实验。每周量小鼠体重,动态观察小鼠体重变化。代谢笼中测量小鼠饮食水量变化。结果模型组血糖较普食组显著上升（P〈0.01）,且维持较好;血脂指标CHO、HDL-c、LDL-c均较普食组升高（P〈0.05）;其他各检测生化指标差异不显著。小檗碱组空腹血糖较模型组总体下降趋势明显且维持较好（P〈0.01）;血脂较模型组有降低;糖耐量胰岛素耐量较模型组有改善。二甲双胍组血糖较模型组有下降趋势,血脂较模型组无显著差别。小檗碱加低剂量添加剂组较模型组血糖血脂无显著差别。小檗碱加高剂量添加剂组血糖较模型有下降趋势,血脂较模型组有下降趋势,其他各项生化指标均无差别。结论小檗碱降糖效果优于二甲双胍,小檗碱加低剂量添加剂,小檗碱加高添加剂。     

Risk and mechanism of glucose metabolism disorder in the offspring conceived by female fertility maintenance technology

Although female fertility maintenance technology (FFMT) provides an effective option for preserving fertility in patients with cancer suffering from fertility loss due to cancer treatment, previous studies have shown that the technique has certain potential risks and requires an assessment of the health status of the offspring since FFMT may lead to glucose metabolism disorder in offspring mice. The present animal study examined the glucose metabolism of adult mice offspring born from ovarian tissue cryopreservation and orthotopic allotransplantation. The mice were divided into three groups: normal, fresh ovary transplantation, and cryopreserved ovary transplantation. We recorded fasting blood glucose, glucose tolerance, and fasting serum insulin level for six months. Liver DNA, RNA, and proteins were extracted to detect the interaction between DNA methylation and Grb10 expression and insulin signaling pathway factors such as P-IGF1R, P-IRS2, P-AKT, and Grb10. Female recipient mice that received FFMT could successfully give birth after mating. The average litter size and total litter size of the cryopreserved and fresh groups showed marked differences compared with the normal group. Compared with the normal group, the fasting blood glucose and fasting serum insulin levels were higher in the cryopreserved and fresh groups. The mRNA and protein expressions of Grb10 were higher in the fresh and cryopreserved groups. Compared with the normal group, the DNA methylation status of four of the 11 sites of the Grb10 promoter was lower in the cryopreserved group. Grb10 overexpression inhibited the downstream phosphorylation protein factor expression (p-IGF-1R, p-IRS2, and p-Akt) of the IGF-1R signaling pathway. Female fertility maintenance technology (FFMT), including ovarian tissue cryopreservation (OTC), and orthotopic allotransplantation techniques might lead to glucose metabolism disorders in offspring mice.     

实验性2型糖尿病恒河猴模型的构建及其部分临床特征分析

目的构建2型糖尿病（T2DM）恒河猴模型,使之成为研究人类T2DM的有效替身。方法以高糖高脂饮食为基础,在出现高脂血症和肥胖状态后注射35mg／kg的链脲佐菌素（STZ）,测定体重指数、血脂、空腹血糖、胰岛素、胰岛素抵抗指数、尿糖和口服葡萄糖耐量试验等,分析其部分临床特征。结果T2DM模型组体重指数（BMI）大于35达到重度肥胖,有高脂血症的特点,空腹血糖、胰岛素和胰岛素抵抗指数显著增高（P〈0．01）,尿糖检测呈阳性,葡萄糖耐量受损并且空腹血糖高于7mmol／L、2h的血糖水平高于11．Immol／L,胰岛有轻度损伤和病变。结论通过部分临床特征分析,T2DM模型组具有典型的T2DM临床特征,可成为T2DM研究的有效模型。     

Beneficial effect of vitamin E on the metabolic parameters of diabetic rats

The role of vitamin E in the pathogenesis of diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin E on some of the metabolic parameters of experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight at 12 weeks of age). Vitamin E (0.2, 0.4, 0.8 mg/kg body weight) was administered orally for a period of 3 weeks to normal and diabetic Wistar rats. In some experiments, Vitamin E was given either before or after the induction of diabetes mellitus. Blood glucose level and weight were recorded for each rat in different groups on a weekly basis. Oral glucose tolerance test (OGTT) was performed on fasted normal, diabetic and vitamin E treated rats at the end of the experiment. Vitamin E significantly (p < 0.01) reduced blood glucose levels in experimental diabetes mellitus at all doses as compared to untreated rats. Vitamin E induced weight loss in normal as well as in diabetic rats. The beneficial effect of vitamin E on the hyperglycaemia of diabetic rats was dose-dependent. Moreover, vitamin E also improved OGTT in diabetic rats compared to untreated diabetics. In conclusion, vitamin E may play a role in glucose metabolism and thus be a useful adjuvant therapy in type I diabetes. (Mol Cell Biochem 261: 35–42, 2004)     

Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol-fed rats: Role of polyprenyl derivatives and nitric oxide

Sodium selenate, administered intraperitoneally (i.p.), resulted in an improvement in glucose tolerance in treated diabetic rats. Fed rat plasma glucose levels were reduced by selenate treatment in streptozotocin diabetic rats. The lowest values of blood glucose were reached within 3 weeks of beginning the treatment. Food and fluid consumption was reduced in treated compared to untreated diabetic rats. Diabetic treated rats did not release insulin in response to a glucose challenge and insulin release in response to a challenge was markedly reduced in control treated rats. Assessment of heart function using a working heart apparatus showed that treated diabetic rats with improved blood glucose levels had normal heart function at 8 weeks of diabetes in contrast to hearts from non-treated diabetics. This study extends previous observations on the in vivo insulin-like effects of sodium selenate.     

Streptozotocin diabetes in juvenile pigs. Evaluation of an experimental model

Spontaneous diabetes in the domestic pig, an animal suitable for metabolic and endocrine studies and for experimental surgery, is extremely rare. In this study we have compared the diabetogenic response of various doses of streptozotocin in comparison to surgically induced diabetes. Streptozotocin in a low dose, 35 mg/kg body weight did not influence glucose metabolism while an intermediate dose, 85 mg/kg, resulted in a transient diabetic reaction. Streptozotocin, 100-150 mg/kg body weight, caused a complete and permanent diabetes. Animals made diabetic by means of pancreatectomy did not survive more than 10 days due to their poor general condition and diabetes. Streptozotocin induced diabetic animals survived with insulin treatment up to seven months. The results show that juvenile pigs made diabetic with 100-150 mg/kg body weight of streptozotocin may be useful in experimental work on glucose-, insulin- and C-peptide-metabolism in a large animal. Therefore it is potentially useful in pancreatic transplantation research.     

Antidiabetic activity of Taxus cuspidata polysaccharides in streptozotocin-induced diabetic mice

In present study, crude polysaccharides (TCPs) were obtained by hot water extraction and ethanol precipitation from the Taxus cuspidata. With a purpose of finding valuable and economical drug for diabetes, TCPs was administered orally at three doses [50, 100 and 200 mg/kg body weight (b.w.)] to the diabetic mice induced by streptozotocin (STZ). The body weight, fasting blood glucose (FBG), fasting serum insulin (FINS), lipid peroxidation and superoxide dismutase (SOD) activity, as well as glucose tolerance were evaluated in normal and STZ-induced diabetic mice. TCPs could dose-dependently significantly increase the body weight of diabetic mice, and reverse the decrease of SOD and the increase of thiobarbituric acid reactive substances (TBARS) in kidney and liver of diabetic mice as compared to those in control group. Meanwhile, the level of FBG markedly decreased in diabetic mice administrated with TCPs, followed by the enhancement of FINS level especially at the higher dose. Furthermore, glibenclamide and TCPs significantly suppressed the rise in blood glucose after 30 min in the acute glucose tolerance test. These results indicated that TCPs could be developed to a potential anti-diabetic drug in the future.     

Effect of melatonin on vascular reactivity in pancreatectomized rats

The present study was undertaken to assess whether the improvement of contractile performance of aortic rings by melatonin described in streptozotocin diabetic rats also occurs in another model of type I diabetes, the pancreatectomized rats. Adult male Wistar rats submitted to a subtotal pancreatectomy and exhibiting altered levels of fasting glucose and an abnormal tolerance glucose test, were used. Sham-operated laparotomized rats were employed as controls. Dose-response curves for acetylcholine-induced, endothelium-related relaxation of aortic rings (after previous exposure to phenylephrine) and for phenylephrine-induced vasoconstriction were conducted. This protocol was repeated with rings pre-incubated in a high glucose solution (44 mmol/l). Pancreatectomy decreased significantly acetylcholine-induced relaxation of aortic rings, but not phenylephrine-induced vasoconstriction, the effect being amplified by preincubation in high glucose solution. The deleterious effect of a high glucose medium was more pronounced in pancreatectomized rats. Melatonin (10(-5) M) did not modify acetylcholine-induced relaxation in normal glucose concentration but was effective to prevent the impairment of relaxation brought about by exposure to high glucose solution. The contractile response to phenylephrine of aortic rings obtained from pancreatectomized rats was not affected by melatonin. The results further support the improvement by melatonin of endothelial-mediated relaxation in blood vessels of diabetic rats.     

人脐带间充质干细胞移植对糖尿病大鼠血清学的影响

目的:观察人脐带间充质干细胞(hu MSCs)移植对糖尿病大鼠血糖、胰岛素和血清因子表达的影响。方法:随机选择12只Wistar大鼠通过腹腔注射链脲佐菌素50 mg/kg,血糖高于16.7 mmol/L者定为糖尿病大鼠,再将其随机分为糖尿病组和干细胞组,每组6只,同时选择6只雄性Wistar大鼠为正常组。干细胞组大鼠腹腔注射hu MSCs细胞悬液,糖尿病组注射PBS液。分别于注射2周、4周和6周后测定和比较各组大鼠的血糖、血清胰岛素、肿瘤坏死因子(TNF-α)和白介素-6(IL-6)的表达。结果:与正常组比较,糖尿病组和干细胞组大鼠的血糖水平均显著升高,胰岛素水平均显著降低(P0.01)。与糖尿病组比较,干细胞组大鼠注射hu MSCs后的血糖水平明显降低,胰岛素水平明显升高(P0.05),血清TNF-α和IL-6 m RNA水平均显著降低(P0.01)。结论:hu MSCs移植能显著降低糖尿病大鼠的血糖,促进其胰岛素分泌,同时降低血清TNF-α和IL-6的表达。     

Altered tail-skin temperature responsiveness in streptozotocin-induced diabetic rats

We evaluated the tail-skin temperature response to administration of several doses of isoproterenol in streptozotocin-induced diabetic rats after 48 h and after 4 weeks of diabetes. Blood glucose concentrations were significantly increased over controls 48 hours after administration of streptozotocin (65 mg/kg, i.v.) and remained elevated to a similar degree in the 4-week group. Basal rectal temperature and tail-skin temperature (TST) were not different between controls and the diabetic groups and were not affected by administration of saline. However, administration of isoproterenol (25 micrograms/kg, s.c.) caused a significant rise in TST in the control group, but not in the rats diabetic for 4 weeks. A similar but exaggerated response was observed in the controls after subcutaneous administration of 40 micrograms/kg and 100 micrograms/kg of isoproterenol. The TST response in the 4-week diabetic rats still remained negligible with the two higher doses of isoproterenol. When the data were summarized as area under the TST curve, a dose-dependent increase was observed in the control groups and a significant absence of response was observed in the 4-week group. The rats studied 48 h after streptozotocin injection had a similar TST response to the control group after administration of 40 micrograms/kg of isoproterenol. Colonic temperatures did not significantly change between the two groups in any of the studies, although the colonic temperatures tended to rise in the control groups following administration of isoproterenol. We conclude from this study that the absence of a tail-skin temperature response in rats diabetic for 4 weeks results from either a reduced beta-adrenergic receptor mediated response or an altered neural thermoregulatory reflex response, or both. These changes are probably not due to streptozotocin treatment or increases in blood glucose.     

Maternal low-carbohydrate high-protein diet affects mandibular growth in diabetic newborn rats

Dams with 7 pups each were randomly assigned to two different diets. Twelve dams were fed a normal (20%) protein diet and were divided into two groups of 4 and 8 animals. Pups from group 1 (n = 28) were injected with citrate buffer as a control. Pups from group 2 (n = 56) were injected with streptozotocin. Twelve additional dams were fed a 40% protein diet. They were also divided into two groups of 4 and 8 animals. Pups from group 3 (n = 28) were injected with citrate buffer as a control. Pups from group 4 (n = 56) were injected with streptozotocin. Forty-eight hours later, diabetic status was determined using Dextrostix. On Day 15, pups were injected with [14C]proline to determine collagen synthesis and 45Ca to study mineralization. After the pups were killed, blood glucose levels were determined. Then mandibles were removed. Milk from each dam was also collected after injection of oxytocin. At the time of killing, blood glucose levels in diabetic pups were less than earlier levels, though still higher than those of controls on either diet. The weights of body and mandible, collagen contents, and the total calcium contents in the diabetic group were in general less than those of the nondiabetic group on the 20 and 40% protein diets. 45Ca uptake in the diabetic group was significantly increased compared with those of the nondiabetic rats on both diets. The percentage reduction in the mandibles of diabetic rats from those of nondiabetic rats on the 40% protein diets was consistently less than that of animals on the 20% protein diets. The higher protein contents of the maternal milk in the 40% protein group may partly be responsible for the smaller impairment of mandibular development in the diabetic over nondiabetic animals. It is concluded that maternal low-carbohydrate high-protein diets will play indirectly a beneficial role in the development of the mandibles of diabetic newborns.     

2型糖尿病伴发高血压大鼠模型的建立

目的：建立一种2型糖尿病伴发高血压大鼠的模型。方法：65只SD雄性大鼠,随机分为正常对照组、1% NaCl饮水组、20 mg/kg STZ-1% NaCl组、30 mg/kg STZ-1% NaCl组、40 mg/kg STZ-1% NaCl组（n=13）。除正常对照组大鼠普通饮食喂养外,其余各组大鼠以高脂饲料4周+普通饲料结合1% NaCl饮水9周喂养。第4周末链脲霉素（STZ）组大鼠分别腹腔注射STZ （20 mg/kg、30 mg/kg、40 mg/kg）。实验周期13周。检测大鼠一般状况、体重、平均摄食量、血糖、血压、血脂和血浆胰岛素水平。结果：与正常对照组和1% NaCl饮水组比较,在STZ注射后仅30 mg/kg STZ-1% NaCl组、40 mg/kg STZ-1% NaCl组大鼠体重减少（P<0.05）、平均食量、空腹和随机血糖均增加（P<0.05）;第4周起血压显著升高（P<0.05）,收缩压均值达到150 mmHg进入高血压期,并在其后5周（实验结束前）稳定于150~170 mmHg;第9周血浆胰岛素水平升高（P<0.05）,血浆甘油三酯（TG）水平下降（P<0.05）。结论：高脂饲料喂养4周+腹腔注射STZ 30~40 mg/kg结合1% NaCl饮水喂养,能诱导出2型糖尿病伴发高血压的大鼠模型。     

Pretreatment Effect of Resveratrol on Streptozotocin-Induced Diabetes in Rats

This study was planned to investigate the pretreatment effect of resveratrol on streptozotocin-induced diabetic rats. The control group consisted of 10 male albino Sprague–Dawley rats, 10–12 weeks of age, weighing approximately 295 g. The first experimental group consisted of 15 albino Sprague–Dawley rats, 10–12 weeks of age, weighing approximately 305 g. This group was administered streptozotocin (55 mg/kg, intraperitoneally). The second experimental group (n = 15) was administered resveratrol (0.5 ml/day) 10 days before streptozotocin induction. A training period was performed for all groups before the experimental procedure, and systolic arterial blood pressures and heart rates were recorded daily. At the end of the 10th day, blood samples of control and experimental groups were drawn. Total nitrite, nitrite, nitrate, malondialdehyde (MDA), copper, and zinc concentrations in plasma were measured both in control and experimental groups. Additionally, superoxide dismutase, catalase activities, and copper and zinc concentrations in red cell were determined in each group. At the end of the study, increases in catalase activity, nitric oxide level, and zinc concentrations and decreases in lipid peroxidation product MDA and copper concentrations were found in the resveratrol-pretreated diabetic group when compared to the diabetic group. This study was presented at “The 5th International Congress of Pathophysiology (ISP2006)” June 28–July 1, 2006, Beijing, China.